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Biomedical subjects

K Tamura

Publications and source records attributed to K Tamura.

At least 91 records · Page 5Linked to original sources

Ehlers-Danlos syndrome type IV with a unique point mutation in COL3A1 and familial phenotype of myocardial infarction without organic coronary stenosis.

We report on a 43-year-old male patient with Ehlers-Danlos syndrome (EDS) type IV with acute myocardial infarction (MI) without organic coronary stenosis. The disease was complicated with pneumothorax, subcutaneous and mediastinal emphysema, and splenic artery rupture. Three of the patient's family members suffered sudden cardiac death or MI. A diagnosis of EDS type IV was confirmed by decreased production of type III collagen by 86%. Mutation analysis revealed a point mutation in the COL3A1 gene that substituted glycine for aspartate at amino acid position 877. This mutation had not been reported as pathogenic for EDS type IV. These findings suggest close linkage between the mutation and the phenotype with familial MI.

Adult↗

Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity.

Tumor cells often express phenotypic markers that are specific to the cells from which they originated. A neural RNA-binding protein, Musashil, is an evolutionarily well-conserved marker for neural stem cells/ progenitor cells. To examine the origin of gliomas, we examined the expression of the human Musashil homolog, MSI1, in human glioma tissues and in normal human adult and fetal brains. As we had seen previously in rodents, in the normal human brain, MSI1 was expressed in cells located in the ventricular and subventricular zones, in GFAP-negative glial cells, and in GFAP-positive astrocytes. In glioblastomas, MSI1 was expressed in GFAP-negative tumor cells forming foci that were clearly demarcated and surrounded by GFAP-positive cells. Tumor cells arranged in pseudopalisades were also strongly immunoreactive with MSI1 antibodies. The percentage of MSI1-labeled tumor cells increased in higher-grade astrocytomas and correlated with proliferative activity, as estimated by an MIB-1 staining index. Our results indicate that MSI1 is an excellent marker for neural progenitor cells including neural stem cells in normal human brains. Furthermore, the expression of MSI1 correlates well with the immature nature as well as the malignancy of tumor cells in human gliomas. Thus, we expect the analysis of MSI1 expression to contribute to the understanding of the cellular origin and biology of human gliomas.

Adult↗

Fibroblast growth factor-induced gene expression and cartilage pattern formation in chick limb bud recombinants.

To clarify the roles of fibroblast growth factors (FGF) in limb cartilage pattern formation, the effects of various FGF on recombinant limbs that were composed of dissociated and reaggregated mesoderm and ectodermal jackets were examined. Fibroblast growth factor-soaked beads were inserted just under the apical ectodermal ridge (AER) of recombinant limbs and the recombinant limbs were grafted and allowed to develop. Control recombinant limbs without FGF beads formed one or two cartilage elements. Recombinants with FGF-4 beads formed up to five cartilage elements, which were aligned along the anteroposterior (AP) axis. Each cartilage element showed digit-like segmentation. In contrast, recombinants with FGF-2 beads showed formation of multiple thick and unsegmented cartilage rods, which elongated inside and outside the AP plane from the distal end of the recombinants. Recombinants with FGF-8 beads formed a truncated cartilage pattern and recombinants with FGF-10 beads formed a cartilage pattern similar to that of the control recombinants. The expression of the Fgf-8, Msx-1 and Hoxa-13 genes in the developing recombinant limbs were examined. FGF-4 induced extension of the length of the Fgf-8-positive epidermis, or AER, along the AP axis 5 days after grafting, at which time the digits are specified. FGF-2 induced expansion of the Msx-1-positive area, first in the proximal direction and then along the dorsoventral axis. The functions of these FGF in recombinant and normal limb patterning are discussed in this paper.

Animals↗

Effects of CP-060S, a novel cardioprotective drug, in the methacholine-induced ECG change model in rats.

We compared the antianginal effect of CP-060S, a novel cardioprotective drug with Na+ and Ca2+ overload-preventing activity as well as Ca2+ channel antagonistic activity, with that of diltiazem, in an experimental model of vasospastic angina induced by methacholine in anaesthetized rats. Intra-aortic injection of methacholine at the coronary ostium provoked the ST-segment elevation of the electrocardiogram (ECG), indicating myocardial ischemia. CP-060S (3, 5 and 10 mg/kg, i.d.) significantly and dose-dependently suppressed the methacholine-induced ST-elevation, with the duration of action being at least 3 h at the highest dose. In addition, CP-060S at 3 mg/kg could inhibit the ST-elevation without producing significant changes in blood pressure, heart rate or rate-pressure product (RPP). In contrast, diltiazem (10 and 30 mg/kg, i.d.) significantly decreased the RPP, a significant suppression of the ST-elevation could only be achieved at the highest dose and its duration of action was about 2 h. Similar results were obtained with i.v. administration of the drugs, i.e. CP-060S given i.v. could inhibit the ST-elevation with less haemodynamic changes than diltiazem. In conclusion, CP-060S exerted a more potent and sustained protection against myocardial ischemia evoked by methacholine than diltiazem. The characteristics of the effects of CP-060S observed here suggest that this drug may be a desirable drug for the treatment of vasospastic angina.

Anesthesia↗

Evaluation of the autonomic nervous system function in children with primary monosymptomatic nocturnal enuresis--power spectrum analysis of heart rate variability using 24-hour Holter electrocardiograms.

OBJECTIVE: The purpose of this study was to evaluate the circadian rhythm of the autonomic nervous system functions of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: The subjects were allocated to three groups--enuresis group (n = 72), normal control group (n = 26), post-treated and cured enuresis group (n = 13). In the three groups. we evaluated the autonomic nervous system function by the power spectrum analysis of heart rate variability (HRV) using 24-hour Holter electrocardiograms. Frequency components of the power spectra of HRV (% power) were divided into three factors; the very low frequency (VLF), the low frequency (LF) and the high frequency (HF) by computer analysis using Fast Fourier Transformation (FFT). RESULTS: In the three groups, the HF component reflecting parasympathetic activity was significantly higher, compared with the LF during sleep. The HF in the enuresis group was significantly higher, compared with the HF in the control group during sleep. The HF in the control group was significantly lower, compared with the LF during waking. However, the HF in the enuresis group was significantly higher, compared with the LF during waking. It showed more increased parasympathetic tone in the enuresis group, compared with that of the control group during sleep and waking. In the post-treated enuresis group, the HF during sleep and waking were significantly decreased, compared with those before treatment. CONCLUSION: These findings suggest the parasympathetic hyperfunction through 24 hours and abnormal circadian rhythm of autonomic nervous system functions in the enuresis group. The post-treated enuresis group showed normal autonomic nervous system functions.

Autonomic Nervous System↗

Effects of the inhalation of diesel exhaust, Kanto loam dust, or diesel exhaust without particles on immune responses in mice exposed to Japanese cedar (Cryptomeria japonica) pollen.

To assess the potential enhancement by air-pollutants of immune responses in mice, especially with regard to allergen-specific immunoglobulin E (IgE) antibody production, female BDF(1) mice (60 mice in each group) were exposed to diesel exhaust (particles, 3.24 mg/m(3); nitrogen dioxide, 1.0 ppm: DE group), Kanto loam dust (particles, 3.29 mg/m(3); nitrogen dioxide, 0.01 ppm: KLD group), diesel exhaust without particles (particles, 0.01 mg/m(3); nitrogen dioxide, 1.1 ppm: DEG group), or clean air (pollen and control groups) for 16 h/day, 5 days/wk for 24 wk, as well as to Japanese cedar pollen (JCP) (around 550,000 grains of JCP/m(3)) for 2 days/wk in the same period. The control group was exposed to clean air alone throughout the experiment. The mean values for Japanese cedar pollen allergens (JCPAs)-specific immunoglobulin E (IgE) antibody titers in mice sera measured by enzyme-linked immunosorbent assay (ELISA) in the DE, KLD, and DEG groups were higher than that for the pollen alone group, but not significantly, after both 12 and 24 wk of exposure time. The percentages of animals expressing more than the minimum ELISA titer of JCPAs-specific IgE antibodies in each group were 22% (DE and pollen groups) and 27% (KLD and DEG groups) of the totals at wk 12, and no statistical differences were observed among the groups. However, at wk 24 in the DE, KLD, and DEG groups the responders comprised 73%, 63%, and 67%, respectively, significantly higher than the 33% for the pollen alone group. No significant differences were observed among the DE, KLD, and DEG groups. A slight dose-dependent increase of proliferative responses of mouse cervical lymph node cells to JCPAs in both DE and KLD groups was observed, but not in the DEG group. Remarkable decrease of interferon-gamma and significant increase of interleukin-4 in the nasal lavage fluid were apparent after DE or DEG exposure, but not in the KLD group. These results suggest that these air pollutants (DE, KLD, and DEG) enhance the production of IgE antibodies in mice, with similar adjuvant activities in each case. Furthermore, in the early phase of exposure in which sensitization occurred with exposure to pollen, the fine particles and gas components are considered to have exhibited different enhancing mechanisms in mice as follows: (1) The fine particles augmented production of IgE antibodies through activation of T lymphocytes, and (2) the gas components exhibited almost no action on T lymphocytes, but directly induced disorders of the cytokine network and augmented the production of IgE antibodies.

Air Pollutants↗

T lymphocyte activation and restenosis after percutaneous transluminal coronary angioplasty.

We investigated the relation between the activation of T lymphocytes and the occurrence of restenosis after percutaneous transluminal coronary angioplasty (PTCA) in 10 stable angina patients. Recent studies have suggested that PTCA causes an inflammatory response, which may affect restenosis after angioplasty. Soluble interleukin-2 receptor (sIL-2R) is a useful marker to evaluate the activation of T lymphocytes. sIL-2R was measured before and 2 h after successful PTCA, and 3-month follow-up coronary angiography was done to observe restenosis. Four of 10 patients showed restenosis. The restenosis group of 4 patients had a higher level of sIL-2R after PTCA than the no-restenosis group of 6 patients (495 vs. 274 U/ml, p < 0.01). This study suggests that sIL-2R may offer prognostic information after elective PTCA and identify a subgroup of patients at high risk for clinical restenosis in a few months.

Aged↗

MEGA2: molecular evolutionary genetics analysis software.

UNLABELLED: We have developed a new software package, Molecular Evolutionary Genetics Analysis version 2 (MEGA2), for exploring and analyzing aligned DNA or protein sequences from an evolutionary perspective. MEGA2 vastly extends the capabilities of MEGA version 1 by: (1) facilitating analyses of large datasets; (2) enabling creation and analyses of groups of sequences; (3) enabling specification of domains and genes; (4) expanding the repertoire of statistical methods for molecular evolutionary studies; and (5) adding new modules for visual representation of input data and output results on the Microsoft Windows platform. AVAILABILITY: http://www.megasoftware.net. CONTACT: s.kumar@asu.edu

DNA↗

Characterization of an Arabidopsis cDNA encoding a subunit of serine palmitoyltransferase, the initial enzyme in sphingolipid biosynthesis.

Serine palmitoyltransferase (SPT; EC 2.3.1.50) catalyzes the condensation of serine with palmitoyl-CoA to form 3-ketosphinganine in the first step of de novo sphingolipid biosynthesis. In this study, we describe the cloning and functional characterization of a cDNA from Arabidopsis thaliana encoding the LCB2 subunit of SPT. The Arabidopsis LCB2 (AtLCB2) cDNA contains an open reading frame of 1,467 nucleotides, encoding 489 amino acids. The predicted polypeptide contains three transmembrane helices and a highly conserved motif involved in pyridoxal phosphate binding. Expression of this open reading frame in the Saccharomyces cerevisiae mutant strains defective in SPT activity resulted in the expression of a significant level of sphinganine, suggesting that AtLCB2 cDNA encodes SPT. Southern blot analysis and inspection of the complete Arabidopsis genome sequence database suggest that there is a second LCB2-like gene in Arabidopsis. Expression of a green fluorescent protein (GFP) fusion product in suspension-cultured tobacco BY-2 cells showed that AtLCB2 is localized to the endoplasmic reticulum. AtLCB2 cDNA may be used to study how sphingolipid synthesis is regulated in higher plants.

Acyltransferases↗

Synergistic interaction of integrin and angiotensin II in activation of extracellular signal-regulated kinase pathways in vascular smooth muscle cells.

Integrins, major adhesion receptors and angiotensin II activate extracellular signal-regulated kinase (ERK) pathways and result in a mitogenic response such as the proliferation of vascular smooth muscle cells (VSMCs). We investigated mechanisms of collaboration or synergism between integrins and angiotensin II involving ERK pathways in VSMCs. Integrin activation by cell adhesion to fibronectin increased the phosphorylation level of focal adhesion kinase (FAK) upstream of the ERK pathway. angiotensin II induced a high increase in the phosphorylation level of FAK with integrin activation, but not in suspended cells. Integrin activation increased phosphorylation levels of ERK kinase (MEK) and ERK phosphorylation as well. Angiotensin II-induced MEK and ERK phosphorylation were retained even in suspended cells. Furthermore, with integrin activation, angiotensin II induced a much larger increase in the phosphorylation levels of MEK and ERK. These results suggest that simultaneous stimulation of integrin and angiotensin II receptors cause synergistic interaction in the activation of ERK pathway, possibly via phosphorylation of FAK, which may play a critical role in angiotensin II-mediated mitogenic response in VSMCs.

Angiotensin II↗

Apoptosis and expression of Bcl-2 and Bax proteins in invasive ductal carcinoma of the pancreas.

The Bcl-2 family of genes plays important roles in the regulation of apoptosis. The present study was designed to assess the clinicopathologic significance of apoptosis and the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. The present study included 66 IDCs that were resected between 1982 and 1998. Apoptosis was assessed by the in situ nick end labeling method and pBcl-2 and pBax were stained immunohistochemically. Apoptosis was quantified as the apoptotic index (AI, the percentage of apoptotic cells of the total tumor cells), and a high AI (>10%) was observed in 26 of the 66 (39%) IDCs. The AI correlated significantly with the extent of nodal involvement. pBax immunoreactivity was detected in 42 of 66 IDCs (64%), and pBax expression was significantly correlated with female gender and showed a significant negative correlation with the extent of nodal involvement. pBcl-2 was expressed in 16 IDCs (24%) but did not show any correlation with the clinicopathologic factors. The AI did not correlate with the expression of pBcl-2 or pBax, but there was a significant correlation between the expression of pBcl-2 and that of pBax; 15 of the 16 pBcl-2(+)IDCs were also pBax(+), and only one pBcl-2(+)IDC was pBax(-). Univariate analysis demonstrated that the degree of apoptosis had no significant influence on the patients' prognosis, pBax or pBcl-2 expression was significantly associated with a better prognosis, and in particular, the pBax(+)pBcl-2(+) group had a significantly higher survival than the other groups. On the other hand, the survival curve of the adjuvant chemotherapy (ACT) group was also higher than that of the surgery alone (SA) group, with borderline statistical signfiicance. The ACT group showed a significantly better survival rate than the SA group for the pBax(+)IDC patients, but the AI and pBcl-2 expression were not correlated with an improved survival rate in the ACT group. Multivariate analysis showed that the AI. pBcl-2 expression, and pBax expression by themselves did not represent significant variables for death owing to IDC, but pBax expression was significantly associated with the efficacy of ACT. In conclusion, pBax expression may be essential for pBcl-2 expression. pBcl-2 and pBax expressions are not significant prognostic factors for patients with IDC, but pBax expression may be beneficial in predicting the effects of ACT on patients with IDC.

Adult↗

Antibiotic susceptibilities of Salmonella enterica serovar Typhi and S. enterica serovar Paratyphi A isolated from patients in Japan.

The antibiotic susceptibilities of 62 strains of Salmonella enterica serovar Typhi and 37 strains of S. enterica serovar Paratyphi A were investigated with 18 antibiotics. Eighteen S. enterica serovar Typhi isolates and five S. enterica serovar Paratyphi A isolates were resistant to one or more antimicrobial agents, among which 10 S. enterica serovar Typhi isolates were nalidixic acid resistant and also showed decreased ciprofloxacin susceptibility.

Anti-Bacterial Agents↗

Characterization of multidrug-resistant Salmonella enterica serovar Typhimurium isolated in Japan.

A total of 221 isolates of multidrug-resistant Salmonella enterica serovar Typhimurium in Japan were characterized in the present study. The results revealed that clonal serovar Typhimurium definitive phage type 104 strains prevailed and that these strains had drug resistance patterns, integron types, and pulsed-field gel electrophoresis patterns similar to those predominant among isolates in Western countries.

Animals↗

Helicobacter pylori infection increases mucosal permeability of the stomach and intestine.

It is important to study the effect of Helicobacter pylori infection on the permeability of the intestine. Permeability was evaluated by oral sucrose tolerance test using sucrose 25 g in 200 ml of water. Existence of H. pylori itself was associated with increased permeability of sucrose. Also, the permeability of sucrose increased as polymorphonuclear and lymphocyte infiltration increased. The increase of mucosal permeability suggests that antigens like protein penetrate into the body and result in systemic reactions. Thus, it is important to study the implication of increased permeability in relation not only to gastric diseases but also certain systemic diseases.

Adult↗

Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor-specific immunity in mice.

OBJECTIVE: The biological activities of interleukin-17 (IL-17), a newly cloned cytokine, have not been fully elucidated. The present study was designed to assess the in vitro and in vivo effect of transfecting the IL-17 gene into tumor cells. METHODS: A complementary DNA (cDNA) encoding human IL-17 (hIL-17) was obtained by polymerase chain reaction amplification from the human CD4+ T cell cDNA library and inserted into the plasmid pRc/cytomegalovirus to construct an expression vector for the hIL-17 gene. Murine Meth-A fibrosarcoma cells were transfected with the hIL-17 gene using the lipofectin method. The hIL-17 gene-expressing clone (Meth-A/IL-17) was selected and analyzed for cytokine expression by Northern blot. RESULTS: There was no significant difference in the in vitro proliferation rate among parent Meth-A, cells transfected with vector alone and Meth-A/IL-17 cells. When the tumor cells were transplanted subcutaneously into BALB/c nude (nu+/nu+) mice, there was no difference in in vivo growth rates among the three cell lines. Challenge with tumor cells in conventional BALB/c mice, however, resulted in the rejection of Meth-A/IL-17 cells, but the other two lines did grow. After immunization with Meth-A/IL-17 cells, the mice were rechallenged by parent Meth-A or syngeneic MOPC-104E plasmacytoma cells; the immunized mice rejected the Meth-A cells, but not the MOPC-104E cells. Injecting the anti-thy 1,2 (CD90), anti-CD4 or anti-CD8 monoclonal antibody into conventional BALB/c mice resulted in the resumption of in vivo growth of Meth-A/IL-17 cells, but injecting the anti-asialo GM1 antibody did not. Furthermore, flow cytometric analysis demonstrated a significant increase in the expression of major histocompatibility complex (MHC) class I and class II antigens and lymphocyte function-associated antigen-1 on Meth-A/IL-17 cells. CONCLUSION: Meth-A cells transfected with the hIL-17 gene can induce tumor-specific antitumor immunity by augmenting the expression of MHC class I and II antigens, and both CD4+ and CD8+ T cells may play important roles in inducing antitumor immunity, suggesting the possibility of developing a tumor vaccine incorporating IL-17-transfected tumor cells.

Animals↗

Successfully treated unstable angina pectoris in a young Japanese female.

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.

Adult↗

Effects of hot bath immersion on autonomic activity and hemodynamics: comparison of the elderly patient and the healthy young.

Hot bathing has been associated with sudden death and so the present study investigated its effects on autonomic activity and hemodynamics in the elderly patient and the healthy young by analyzing heart rate variability (HRV). Subjects were 9 elderly men (mean age, 75 years) and 9 young men (mean age, 27 years), who were immersed up to shoulder level while in a sitting position for 10min with the bath temperature at 40 degrees C. Blood pressure (BP) and heart rate (HR) were monitored. BP in the young decreased during bathing (p<0.01), whereas in the elderly BP had a maximum value just at the start of immersion (p<0.05) with a slight decline at 4 min after the start of immersion. Although HR in the young increased (p<0.01), in the elderly there was an abrupt increase in HR just at the start of immersion (p<0.05), followed by a decrease in HR. With regard to HRV, the high-frequency (HF) component in the young men was suppressed during immersion (p<0.01), but was unaffected in the elderly. The LF (low frequency)/HF ratio in the elderly decreased at 4 min (p<0.05). In conclusion, hypotensive syncope may cause sudden death by drowning during hot bathing, and is a consequence of the decrease in sympathetic tone that develops approximately 4min after immersion.

Adolescent↗

[Blood vessels in normal and abnormal mitral valve leaflets].

UNLABELLED: The incidence and the distribution of blood vessels were examined in normal and abnormal mitral valve leaflets. MATERIALS AND METHODS: Normal valves were obtained from 12 autopsy cases without cardiovascular disease (8 men, 4 women, 33 to 93 years of age). Twenty-one abnormal valves were obtained at the time of mitral valve replacement (12 men, 9 women, 16 to 78 years of age). Clinical and pathological diagnoses were rheumatic valvular disease (RVD: n=8), floppy mitral valve (FMV: n=9), and healed infective endocarditis (HIE: n=4, 1 with RVD, 3 with FMV). The number of vessels was counted at the surgical excision line of the valvular rings by immunohistochemical study using Factor VIII related antigen and CD34. Histologic studies were also made at the 5 mm distal line from the ring in normal valves, and at the vertical line to the ring in abnormal valves. RESULTS: In normal valves, the number of vessels at the ring area, except in myocardial tissues that extended from the left atrium to the auricularis, ranged from 3 to 184. Vessels were also found at the 5 mm distal area from the ring in 6 valves out of 12. Vessels were mainly distributed near the commissure areas of the auricularis and/or the spongiosa and were extended with myocardial tissues. There was no difference in the number of vessels related to age or sex. In RVD, the number of vessels at the ring area ranged from 22 to 517 in 8 anterior leaflets (AML) and 2 to 151 in 5 posterior leaflets (PML). Many vessels also appeared in the distal spongiosa of the leaflets, and arterioles were frequently found in these areas. In FMV, a few (3 and 6) vessels were found in 2 leaflets (AML: 2/8, PML: 0/4). In HIE, the number of vessels was 216 in the case with RVD, and 3 to 110 in cases with FMV. CONCLUSION: At the ring area, normal mitral valve leaflets were supplied with nutrition from blood vessels that mainly extended from the left atrium with myocardial tissues. In RVD, the vessels branched from previously existing capillaries, extending to the distal area, and increased in number. Mechanical stress during opening and closing of the leaflets contributes to the arterialization of these vessels. In FMV, the number of capillaries, which is smaller than in normal valves, might be related to the progression of this disorder. In HIE with valvular disease, the number of vessels is related to the preexisting disease.

Adult↗